Tests On Professional Antiseptics Could Influence Consumer Hand Wash Market

The additional year FDA is allowing for research on the safety of six antiseptic ingredients in health care personnel hand washes could generate data that determine whether three of the ingredients also will remain available in consumer hand rubs.

FDA's Center for Drug Evaluation and Research granted the extension in response to manufacturers' requests for more time to complete research on active ingredients in OTC monograph antiseptic products made for health care personnel: povidone-iodine, isopropyl alcohol, benzalkonium chloride, benzethonium chloride, chloroxylenol and ethyl alcohol.

Three of the ingredients – ethyl alcohol, isopropyl alcohol and benzalkonium chloride – also are being studied by manufacturers, in a separate rulemaking by CDER, to show they are generally recognized as safe and effective (GRASE) for use in consumer antiseptic rubs, which are intended for use without water and also are part of FDA's OTC antiseptic monograph.

GRASE for consumer antiseptic hand wash ingredient benzalkonium chloride, used in products such as Creations Gardens Sanitizer and Greenbrier International's Wet Wipes, or ethyl alcohol or isopropyl alcohol could be shown in testing for health care professional hand wash antispetics.

The extension for health care product testing, which could be renewed, is conditional on the firms starting studies demonstrating the substances are GRASE, the threshold for inclusion in an OTC drug monograph, CDER's Division of Nonprescription Drug Products stated in Jan. 19 letters to the American Cleaning Institute and manufacturers Ashland Global Holdings Inc.'s Ashland Specialty Ingredients business, BASF Corp., Clorox Co., Ecolab USA Inc., GOJO Industries Inc., Lonza America Inc., and Thomas Swan & Co. Ltd.

In the letters posted to FDA’s docket for the antiseptic monograph rulemaking (see table below), the agency says firms must submit a report describing specific progress on the ongoing studies by Dec. 19 and that all reports must contain complete data sets, analysis, assessment and interpretation.

FDA is required under a 2013 consent decree settling litigation by the National Resources Defense Council to publish its final monograph for health care antiseptic products by Jan. 15, 2018. (Also see "Consent Decree Orders FDA Action On Triclosan OTC Monographs" - HBW Insight, 9 Dec, 2013.)

“FDA is prepared to initially defer this ingredient from rulemaking for one year, subject to renewal, to permit these studies to be conducted; however, if no such studies have been commenced, or if the studies in progress do not appear, in FDA’s judgement, to be productive, the agency expects that it will proceed to rulemaking for this ingredient after this initial deferral,” DNDP Director Theresa Michele stated in each of the letters.

In a statement, ACI noted the deferral provides more time to all companies that produce health care antiseptic products containing any of the six ingredients. “These deferrals from regulation, if granted, would apply to the market as a whole, and would allow time for efficacy and safety studies to be conducted to fill data gaps previously identified by FDA,” the trade group said.

Health care antiseptics are hand washes and rubs, surgical hand scrubs and rubs and patient preoperative skin preparations, including pre-injection preparations primarily used by professionals in hospitals, clinics, doctors’ offices, outpatient settings and nursing homes.

FDA

Antiseptic hand washes for health care personnel and for consumers are available OTC, though some ingredients in products intended for professional use are not allowed in consumer washes and those products are provided in much larger containers than consumer product packages.

Industry’s Gap-Fill Proposal Pays Off

In its May 2015 proposal to amend the tentative final monograph for health care antiseptic products, FDA identified data gaps for 11 of 28 active ingredients.

CDER has said emerging science suggests that systemic exposure to some health care antiseptic active ingredients is higher than previously thought and raises potential concerns about the effects of repeated daily exposure to some of the ingredients.

ACI submitted proposed protocols for studies to fill efficacy data gaps for in vitro time-kill assay, minimum inhibitory concentration or minimum bactericidal concentration testing and the trade group and manufacturers also requested more time to allow for study completion. However, more efficacy and safety data are needed, FDA determined.

According to FDA's letters, the same data are needed for each of the six deferred ingredients, but recommendations vary for the types of studies needed to fill the information gaps for different ingredients. All ingredients require nonclinical animal studies – with the exception of ethyl alcohol, which does not require nonclinical animal tests – maximal use trials, resistance testing, in vitro time-kill assay, in vitro minimum inhibitory concentration or minimum bactericidal concentration testing and clinical simulation.

As some studies required for ethyl alcohol, isopropyl alcohol and benzalkonium chloride are the same in both the health care and the consumer hand rub rules, FDA's conclusions on research submitted for the health care products could influence its decisions on consumer products, for which GRASE tests must be completed in June 2017.

However, the consumer product proposal allows a 60-day grace period and firms can request testing deferrals like those granted for health care product studies. With those pathways for additional testing time, it is likely that the consumer product rule will be finalized later after additional testing allowed for health care products is concluded, said Richard Sedlak, ACI's executive vice president for technical and international affairs.

“The agency said the work we do on [ethyl alcohol for health care products] should satisfy the consumer hand rub” data gaps, Sedlak said in an interview.

“So the principle is there to maximize the two,” he added. “But the consumer hand rub rule trails [the health care rule] by roughly a year, or a year and a quarter, so you’ll see the writing on the wall if FDA says, ‘No, I need more data specifically on the consumer hand rubs under the health care rule.'"

There are differences in some research required for the health care or the consumer products.

“For some of the studies, because you have higher frequency of use, or differently used applications in the health care setting versus the consumer settings, the FDA wants some of the studies to represent that,” Sedlak added. “We are working with the agency to maximize synergies,” between the testing for the separate monographs, he said, noting ethyl alcohol as an example.

Under the NRDC consent decree, FDA plans to publish a final monograph for consumer antiseptic rubs by April 15, 2019.

Wash-Off Ingredients Also In Play

In a second rulemaking on consumer products, FDA in September 2016 published a final rule for wash-off antiseptics establishing that 19 active ingredients are not GRASE and must be phased out by Sept. 7, 2017. (Also see "FDA Rule Marks Consumer Antibac Soaps A Possible Endangered Species" - Pink Sheet, 2 Sep, 2016.)

Most consumer antibacterial wash-off products contain one of three ingredients that are among those subject to the rule, benzalkonium chloride, benzethonium chloride and chloroxylenol, which also are among the six deferred in the health care antiseptics rulemaking.

Companies marketing wash-off products with one of the three ingredients have less than a year to submit studies to FDA in support of their GRASE status to remain in the monograph. As the deadline for submission is several months ahead of the health care antiseptic deadline, FDA’s decisions for the wash-off ingredients could indicate whether FDA will accept safety data for the ingredients also being considered for inclusion in the health care and consumer product rules.

No Deferrals For Five Ingredients

No deferrals were granted for the other five active ingredients highlighted in the health care ingredient rule, hexylresorcinol, iodine tincture, iodine topical solution USP, triclosan and triclocarban, and FDA is likely to complete a rulemaking for those ingredients by its 2018 deadline.

Sedlak said he is not aware of any other companies’ plans to file a request for deferrals for those substances.

Triclosan and triclocarban were the focus of NRDC's litigation to remove the ingredients from the market due to evidence suggesting the substances pose endocrine-disruption and other health risks while protecting consumers against microbial threats no better than plain soap and water.

Sedlak said triclosan and triclocarban “are largely formulated out" of consumer products, but some products likely remain available with the ingredients, particularly in the health care space.

The fate of the consumer washes and rubs rulemaking could be up in the air after the Freedom Caucus identified the antiseptic rules among a list of 200 rules passed or established through executive orders during the Obama administration that 36 Republicans recommend striking altogether or changing to lessen industries’ regulatory burden. (Also see "Freedom Caucus Hit List Includes Antibacterial Soap, Supplement Label Rules" - HBW Insight, 20 Dec, 2016.)

The caucus had recommended rescinding or canceling the antiseptic wash and rub rules altogether due to their cost, which are estimated at $106.3m to $402.8m.

Sedlak said legislation to eliminate those rules or rulemakings probably isn't a priority currently in Congress. “We are monitoring, we are watching, but we don’t have a prediction right now where they will go. They seem to be busy on a lot of other things right now,” he said.

Sedlak says ACI’s relationship with FDA is strong. “We’ve been doing this work diligently to support FDA, and they seem to be pleased with what we are working on, and supportive and our dialogue will continue to keep these [products] in health care facilities,” he said.

From the editors of the Tan Sheet.